1. Field of the Invention
This invention involves the use of the antibiotic rubradirin to treat methicillin-resistant (multiply antibiotic resistant) staphylococcal infections in humans and useful domesticated animals.
2. Description of the Related Art
Rubradirin is known, see U.S. Pat. No. 3,335,057.
U.S. Pat. No. 3,335,057 disclosed that rubradirin was useful in treating gram-positive infections including those of Staphylococcus aureus (S. aureus).
Bhuyan et al, in Antimicrobial Agents and Chemotherapy 91 (1964), disclosed that rubradirin had in vitro activity against two clinical strains of S. aureus which were resistant to several antibiotics. However, at that time, resistant S. aureus was not regarded as a clinically significant problem because clinical strains of S. aureus were sensitive to a number of antibiotics including methicillin and could be treated with methicillin. However, the strains originally tested by Bhuyan et al, in a latter study were found to be methicillin sensitive. Now, however, infectious stapylococci have become resistant to many antibiotics including methicillin. This is regarded not only as a theoretical problem but a very real one for the physician. These gram-positive bacteria are commonly referred to as methicillin-resistant S. aureus (MRSA) and methicillin-resistant S. epidermidis (MRSE). In practice, MRSA and MRSE are not only resistant to methicillin, but rather are resistant to multiple antibiotics including all penicillins and cephalosporins. Individual isolates are often resistant to lincosamides, macrolides, aminoglycosides and chloramphenicol. Thus, the laboratory finding that an isolate is methicillin-resistant usually indicates clinical resistance to multiple antibiotics. Multidrug-resistant staphylococci have retained their susceptibility to vancomycin, see Orthopedic Clinics of North America 15, 417 (1984).
Methicillin is a .beta.-lactamase stable, semi-synthetic penicillin derivative and was developed to overcome staphylococcal resistance due to enzymatic inactivation. The drug was introduced in Europe in 1960, and methicillin-resistant strains were recognized soon thereafter, see Annals Intern. Med. 97, 440 (1982). Through the 1960's methicillin resistance appeared to be a rare, naturally-occurring phenomenon, of little clinical significance. Increasing isolation of MRSA became evident in the 1970's, as diverse strains emerged in many parts of the world, and produced serious clinical problems, see Annals Intern. Med. 97, 297 (1982). During this time, few reports of MRSA originated in the United States. However, in the late 1970's and early 1980's it became apparent that MRSA and MRSE were becoming important causes of hospital-acquired (i.e. nosocomial) infections, especially in burn units and intensive care wards. The organisms are of special significance since they frequently cause life-threatening disease, including pneumonia, bacteremia, and endocarditis. The number of effective therapeutic agents is extremely limited.
It has been discovered that rubradirin can successfully be used to treat rubradirin-sensitive, methicillin-resistant staphylococcal infections.